Amyloid-beta protofibrils (Aβ protofibrils) (Aβ protofibrils)

Amyloid-beta (Aβ) protofibrils and related soluble aggregates are intermediate, non-fibrillar assemblies of the Aβ peptide that play a central role in the pathogenesis of Alzheimer's disease (Walsh & Selkoe, 2007, PubMed). These species are formed during the transition from monomeric Aβ to insoluble amyloid plaques and are considered significantly more neurotoxic than the plaques themselves (Benilova et al., 2012, Nature Neuroscience). They exert their pathological effects by disrupting synaptic plasticity, inducing oxidative stress, and promoting the spread of tau pathology throughout the brain (Haass & Selkoe, 2007, Nature Reviews Molecular Cell Biology). Therapeutic intervention focuses on using monoclonal antibodies to selectively recognize and neutralize these soluble aggregates, thereby preventing neuronal damage and slowing the progression of cognitive impairment (Söderberg et al., 2023, Journal of Neurochemistry). Lecanemab is a prominent example of a drug designed with high selectivity for protofibrils over monomers and fibrils (van Dyck et al., 2023, NEJM). The clinical success of such agents underscores the importance of targeting soluble Aβ species as a primary therapeutic strategy in neurodegenerative disease (Eisai Co., Ltd., 2023).

Other names

Amyloid-beta oligomersAβ protofibrilsSoluble Aβ aggregatesAβOAmyloid-beta soluble species

Monoclonal antibodies selectively bind to soluble amyloid-beta protofibrils and oligomers, facilitating their clearance via microglia-mediated phagocytosis and preventing the downstream cascade of neurotoxicity and plaque formation.